We have recently identified HAVcr-1, a surface glycoprotein on African green monkey kidney (AGMK) cells, as a receptor for hepatitis A virus (EMBO J. 15:4282-4269, 1996). Molecular cloning and sequence analysis of HAVcr-1 cDNA from several monkey cell lines showed that this receptor is polymorphic. Monoclonal antibody 190/4, which protected AGMK cells against HAV infection failed to react with HAVcr-1 cloned from BS-C-1 and CV-1 cells. HAVcr-1 human homolog genes were mapped to chromosomes 1, 5, and 19 and shown to be expressed in certain human tissues including liver. It is not known if the HAvcr-1 homologs also functions as an HAV receptors. Transgenic mice expressing HAVcr-1 under the control of the RSV LTR promoter were developed. Three transgenic lines carrying different copies of the HAVcr-1 cDNA were obtained. Transgenic animals were infected with HAV and we are analyzing whether HAV can replicate and cause disease in these animals. This studies may result in a small animal model for pathogenesis of HAV. The interaction of HAV with its cellular receptor will help to understand the mechanisms involved in the pathogenicity of this virus and specific receptor antagonists could be useful therapeutic agents. Furthermore, identification of the HAV cellular receptor may lead to the development of small animal models for HAV infecton. Such a model would be important for the testing of potency of future HAV vaccines and for development of new HAV vaccines.